Chromatin organization drives the search mechanism of nuclear factors.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 10 2023
13 10 2023
Historique:
received:
01
06
2023
accepted:
02
10
2023
medline:
23
10
2023
pubmed:
14
10
2023
entrez:
13
10
2023
Statut:
epublish
Résumé
Nuclear factors rapidly scan the genome for their targets, but the role of nuclear organization in such search is uncharted. Here we analyzed how multiple factors explore chromatin, combining live-cell single-molecule tracking with multifocal structured illumination of DNA density. We find that factors displaying higher bound fractions sample DNA-dense regions more exhaustively. Focusing on the tumor-suppressor p53, we demonstrate that it searches for targets by alternating between rapid diffusion in the interchromatin compartment and compact sampling of chromatin dense regions. Efficient targeting requires balanced interactions with chromatin: fusing p53 with an exogenous intrinsically disordered region potentiates p53-mediated target gene activation at low concentrations, but leads to condensates at higher levels, derailing its search and downregulating transcription. Our findings highlight the role of disordered regions on factors search and showcase a powerful method to generate traffic maps of the eukaryotic nucleus to dissect how its organization guides nuclear factors action.
Identifiants
pubmed: 37833263
doi: 10.1038/s41467-023-42133-5
pii: 10.1038/s41467-023-42133-5
pmc: PMC10575952
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Chromatin
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6433Subventions
Organisme : Worldwide Cancer Research
ID : 22-0116
Pays : United Kingdom
Informations de copyright
© 2023. Springer Nature Limited.
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